In vivo stable isotope studies in three patients affected with mitochondrial fatty acid oxidation disorders: Limited diagnostic use of 1-C fatty acid breath test using bolus technique.

The in vivo oxidation of fatty acids (FA) of different chain length was investigated in three patients with documented mitochondrial FA oxidation disorders: one patient with mild multiple acyl-CoA dehydrogenase deficiency (MADM), one with medium chain acyl-CoA dehydrogenase deficiency (MCAD), and one with carnitine palmitoyltransferase I deficiency (CPT I). Breath tests were performed after oral administration of 1-C butyric, 1-C octanoic, and 1-C palmitic acids. C/C ratio in the expired oxidative end product CO was measured. The cumulative C elimination was calculated and expressed as a percentage of the administered dose. In the MADM patient the influence of carnitine therapy (or deprivation) on the utilization of 1-C palmitic acid was also examined. In the MCAD and CPT I patients, the 1-C butyric, 1-C octanoic and 1-C palmitic acids in vivo oxidation were similar to five healthy controls. In the MADM patient, the oxidation of 1-C butyric and 1-C octanoic acids were normal, whereas the metabolism of 1-C palmitic acid ranged from 33% to 66% of controls. In this patient the serum carnitine level decreased from 60 to 27 μmol/l without carnitine supplementation. Clinically there was mild hypotonia. 1-C palmitic acid oxidation compared to controls was 50%. After 2 further weeks of carnitine deprivation the serum carnitine was 10-15 μmol/l. Clinically he was very hypotonic and had a large liver. 1-C Palmitic acid oxidation was 33%. After 6 weeks of readministration of carnitine ( l-carnitine 100 mg/kg/day p.o.) the serum carnitine was 60 μmol/l and the patient was in good clinical condition. 1-C palmitic acid oxidation was 66% compared to controls. Our study implies that this simple fatty acid breath test is not of diagnostic use for detection of enzymatic defects in FA oxidation disorders. The carnitine dependent 1-C palmitic acid oxidation indicates that this test might be of some value in cases with primary or secondary carnitine deficiencies. [ABSTRACT FROM AUTHOR]